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Objective: To determine the efficacy of acotiamide, an acetylcholinesterase inhibitor, in patients with functional dyspepsia (FD) in a 4-week trial., Methods: A multicentre, randomised, placebo-controlled, parallel-group, phase III trial was carried out, in which patients with FD received 100 mg of acotiamide or placebo three times a day for 4 weeks, with 4 weeks post-treatment follow-up. The primary efficacy end points were global assessment of overall treatment efficacy (OTE) and elimination rate of all three meal-related symptoms (postprandial fullness, upper abdominal bloating and early satiation), as derived from daily diaries. Secondary efficacy end points were individual symptom scores and quality of life. Adverse events were monitored., Results: 52.2% of those receiving acotiamide and 34.8% in the placebo group (p<0.001) were classified as responders according to a global assessment of OTE. Over 4 weeks, the elimination rate for all three meal-related symptoms was 15.3% among patients receiving acotiamide compared with 9.0% in the placebo group (p=0.004). The significant benefit of acotiamide over placebo in OTE and elimination rate was maintained during the 4 week post-treatment follow-up. All other secondary efficacy end points, including quality of life, were significantly improved with 100 mg of acotiamide as compared with placebo. The number needed to treat was 6 for OTE and 16 for symptom elimination rate. The incidence of adverse events was similar between the acotiamide group and placebo group and no significant cardiovascular effects due to treatment were seen., Conclusions: Over 4 weeks, acotiamide significantly improved symptom severity and eliminated meal-related symptoms in patients with FD., Trial Registration Number: http://ClinicalTrials.gov number, NCT00761358.

We describe a case of autoimmune hepatitis diagnosed after acute hepatitis B. The patient was a 65-year-old man admitted because of markedly elevated transaminase level. Laboratory tests showed positive IgM-HBc antibody and a short prothorombin time. He was diagnosed as severe acute hepatitis B due to sexual transmission. He received lamivudine and steroid pulse therapy. Transaminase level increased again after steroid pulse therapy and liver atrophy progressed, so cyclosporine was induced. Liver biopsy was done because of prolonged liver function disorder. Biopsy specimens showed not only centrizonal inflammation but also interface hepatitis and bridging fibrosis, which were characteristic of autoimmune hepatitis. We diagnosed autoimmune hepatitis which became clinically evident after acute hepatitis B. Lamivudine was discontinued 7 months after diagnosis and he is now receiving 3mg prednisolone.

Background. Although many reports concerning the use of endoscopic submucosal dissection (ESD) for esophageal cancer have been published, the feasibility of ESD in elderly patients has not been reported. Therefore, we evaluated the efficacy and safety of ESD for treating early esophageal cancer in elderly patients. Methods. A total of 62 cases (52 men, 10 women; mean age ± standard deviation, 66.5 ± 10.5 years) for which the first resection (first treatment) of esophageal cancer was performed by ESD were identified from 77 consecutive esophageal epithelial cancers in 67 patients treated at our institution from January 2005 to March 2011. Patient characteristics, clinical findings, and outcomes were retrospectively assessed for patients separated into older (aged 75 years and older) and younger (aged under 75 years) groups. Results. No significant differences in specimen size, procedure time, median length of the hospital stay (8 versus 9 days; P = 0.252) or procedure-associated complications (8% versus 27%; P = 0.264) were observed between the older (n = 13) and younger (n = 49) groups. Lesions were completely resected in 12 patients and 44 patients, in the younger and older groups, respectively, and the curative resection rate was 77% and 59%, respectively. There were no deaths attributable to procedure-associated complications. Conclusions. ESD is an effective treatment for early esophageal cancer and is well tolerated by elderly patients.

Background and Aim: Functional dyspepsia (FD) is a common condition seen in primary gastroenterology practice. The present study was conducted to compare the clinical effectiveness of mosapride and teprenone in patients with FD., Methods: Prospective clinical comparative study with random allocation of open labeled medications was performed as a multicenter trial in Japan. 1042 patients presenting symptoms of FD, either with gastric stasis (GSS) and/or epigastric pain (EPS), were enrolled. After initial endoscopic evaluation, medication either with mosapride 5 mg tid or teprenone 50 mg tid was started. Severity and frequency of GSS and EPS, health-related quality of life (HR-QOL) by the SF-36 Japanese version, and patients' compliance to medication was evaluated., Results: Organic lesions were found in 90 patients (9%) in the 1027 patients examined by endoscopy. Among those without any specific lesions detected by endoscopy, gastrointestinal symptoms were resolved within one week after the endoscopy in 264 (28%) patients before initiating medication. 618 patients who remained symptomatic were randomized to medication either with mosapride (n = 311) or teprenone (n = 307). Two-week treatment with mosapride significantly improved GSS and EPS, while teprenone tended to improve only GSS. Mosapride also improved HR-QOL. 91% of patients treated with mosapride favored their medication, while only 52% of patients treated with teprenone favored their medication., Conclusions: Endoscopic evaluation at patients' presentation was effective to find active lesions and to improve FD symptoms. Mosapride was more favorably accepted than teprenone by the patients with sufficient safety and efficacy., (© 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.)

Purpose: Although hepatic perfusion abnormalities have been reported in patients with acute pancreatitis, hepatic perfusion with severe acute pancreatitis (SAP) has not been quantitatively evaluated in humans. Therefore, we investigated hepatic perfusion in patients with SAP using perfusion CT., Materials and Methods: Hepatic perfusion CT was performed in 67 patients with SAP within 3 days after symptom onset. The patients were diagnosed as having SAP according to the Atlanta criteria. Fifteen cases were established as a control group. Perfusion CT was obtained for 54s beginning with a bolus injection of 40 ml of contrast agent (600-630 mgI/kg) at a flow rate of 4 ml/s. Perfusion data were analyzed by the dual-input maximum slope method to obtain hepatic arterial perfusion (HAP) and hepatic portal perfusion (HPP). Finally, we compared HAP and HPP in SAP patients with those in the control group, respectively., Results: Average HAP was significantly higher in SAP patients than in the control group (75.1 ± 38.0 vs. 38.2 ± 9.0 ml/min/100ml; p<0.001). There was no significant difference in average HPP between SAP patients and the control group (206.7 ± 54.9 vs. 204.4 ± 38.5 ml/min/100ml; p=0.92)., Conclusion: Using quantitative analysis on perfusion CT, we first demonstrated an increase of HAP in the right hepatic lobe in SAP patients., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Edwardsiella tarda is a bacterium that is associated with both an asymptomatic oral carrier state and self-limiting diarrhoeal illness in humans. We herein report a case of sepsis and liver abscess caused by E. tarda and review the patients with E. tarda sepsis who presented at our hospital. An 85-year-old woman developed enterocolitis and sepsis caused by E. tarda. She was administered intensive care and thus was able to soon show a good recovery, however, she subsequently developed a liver abscess. During a complicated course, she continued to be treated with antibiotics and after a successful course was discharged on the 44th day after admission.

Background: We performed perfusion computed tomography (P-CT) and angiography of the pancreas in patients with severe acute pancreatitis (SAP) and compared the usefulness of these two methods in predicting the development of pancreatic necrosis., Methods: We compared P-CT and angiography results taken within 3 days after symptom onset in 21 SAP patients. We divided the pancreas into three areas, the head, body, and tail, and examined each area for perfusion defects (via P-CT) and arterial vasospasms (by angiography). Three weeks later, all patients underwent contrast-enhanced CT to determine whether pancreatic necrosis had developed., Results: Of the 21 SAP patients, 16 exhibited perfusion defects, while 17 proved positive for vasospasms in at least one area. Fourteen patients developed pancreatic necrosis. Of the 63 pancreatic areas from the 21 SAP patients, perfusion defects appeared in 25 areas (39.7%), 24 of which showed vasospasms (96.0%). Angiography showed 33 areas with vasospasms (52.4%), of which 24 showed perfusion defects (72.7%). Of the 25 areas with perfusion defects, 21 developed pancreatic necrosis (84.0%). Of the 33 areas with vasospasms, 21 developed necrosis (63.6%). Pancreatic necrosis developed only in the areas positive both for perfusion defects and for vasospasms. No areas without perfusion defect or vasospasms developed pancreatic necrosis. P-CT predicted the development of pancreatic necrosis with significantly higher accuracy than angiography., Conclusion: While both P-CT and angiography are useful in predicting the development of pancreatic necrosis in patients with SAP, P-CT appears to be more accurate for this purpose.

Venous thromboembolism associated with use of a central venous access system is an urgent problem in patients treated with bevacizumab (bev). We investigated the effectiveness of Doppler ultrasound imaging (DUS) in the early detection of catheter-related thrombosis for avoidance of severe venous thromboembolism. Patients with metastatic colorectal cancer received either FOLFOX-4 + bev or FOLFIRI + bev. DUS was performed on the deep venous system for detection of thrombus formation during the initial cycle of treatment, followed by re-evaluation after the third cycle in patients with asymptomatic thrombus formation. All patients were followed up until treatment was interrupted. Median duration of follow-up was 484 days (range 72-574). Among 41 enrolled patients, curable symptomatic thrombosis occurred in one, and asymptomatic thrombosis in 21 (51.2%). Of 21 patients undergoing re-evaluation, thrombi remained without progression in 17 patients, and enlargement in 4 patients. In two of the patients in whom there was progression, pulmonary embolism occurred after the sixth cycle. In the asymptomatic group, no thrombi developed as far as the superior vena cava in any patient. In the cases of progression, thrombotic enlargement was observed in all the 4 patients, with decreased vascular flow in 2. Using DUS, we were able to detect asymptomatic thrombosis in the early cycles of treatment, indicating its potential in the monitoring of venous thrombi. In the event of an enlarging asymptomatic thrombosis developing into the superior vena cava along with decreased vascular flow, careful follow-up and appropriate anticoagulant therapy may be recommended without increased risk of bleeding.

We describe a rare case of advanced gastric cancer with markedly high serum levels of human chorionic gonadotrophin beta subunit (hCG-beta). The patient was a 51-year-old man admitted for a gastric tumor growing extramurally and multiple liver tumors revealed by computed tomography, with chief complaints of abdominal and breast mass. Upper gastrointestinal endoscopy showed gastric cancer of Borrmann type 2 and biopsy specimens showed poorly-differentiated adenocarcinoma. The serum levels of hCG/beta was very high (21, 551. 6 mIU/mL). Pathological examination from liver tumor showed the tumor cells greatly resembled gastric tumor and were immunohistochemically positive for hCG-beta. We diagnosed hCG-beta producing gastric cancer. He received chemotherapy, but died of hepatic failure about 8 months after initial diagnosis. When we see a patient with gynecomastia and the high serum hCG-beta levels, it is important that hCG-beta producing-gastric cancer should be considered as a possible malignant tumor of the stomach.

Inflammatory bowel disease (IBD), especially ulcerative colitis (UC), sometimes accompanies with primary sclerosing cirrhosis (PSC). Primary biliary cirrhosis (PBC) is also a chronic liver disease, but is attributed to an unknown immune abnormality. PBC frequently accompanies various autoimmune diseases, but rarely IBD. We report 2 rare cases of IBD which developed in the course of treatment for PBC. A 64-year-old man had blood in his stool 17 months after he was given a diagnosis of PBC. Colonoscopy revealed erosion and disappearance of the vascular network pattern in the rectum. UC (rectal type) was diagnosed and he received mesalazine, and following which his symptoms improved. A 40-year-old woman developed diarrhea, fever and arthralgia while receiving treatment for PBC. Colonoscopy revealed ileal erosion, a longitudinal ulcer in the ascending colon but only mild rectal inflammation. These findings were atypical of UC, and we therefore diagnosed indeterminate colitis. Her symptoms disappeared as a result of the administration of mesalazine.

We used contrast-enhanced ultrasound using the Sonazoid microbubble contrast agent to diagnose three cases of hepatic angiomyolipoma, which is a rare benign tumor. Some characteristic findings are obtained in the early vascular phase, for example fork-like tumor vessels. However, a variety of findings are seen after the early vascular phase because of microbubbles circulating the vascular enriched tumor.

Malignant mucosal melanoma is a rare condition. Although the head and neck region is the most common site for mucosal melanoma, a melanoma arising in the eustachian tube is rare. Here we present a case of mucosal melanoma arising in the right eustachian tube.

We experienced a rare case of autoimmune pancreatitis with sclerosing cholangitis, retroperitoneal fibrosis and interstitial pneumonia. The patient was a 68-year old man and had abnormal liver function with jaundice. We performed endoscopic retrograde cholangiopancreatography (ERCP) and needle biopsy of the liver and pancreas. We obtained histological findings such as dense infiltration of plasma cells and lymphocytes and remarkable fibrosis and diagnosed AIP. The patient received treatment by prednisolone and thereafter developed bladder cancer and gastric cancer. He has been followed up for 4.5 years with no recurrence.

A 69-year-old man was hospitalized for treatment of a left renal tumor. The tumor had originally been demonstrated as a simple renal cyst 4 years before. However, the size of the tumor decreased, and at the time of hospitalization, the tumor showed a solid, papillary component that was enhanced by contrast medium on computed tomography (CT) and had high signal intensity on T2-weighted magnetic resonance imaging (MRI). We diagnosed this tumor as a cystic renal cell carcinoma of the left kidney, cT1aN0M0, arising from the epithelium of a renal cyst, and performed a left partial nephrectomy. The pathological diagnosis was cavernous hemangioma of the left kidney. Generally, it is difficult to diagnose a cavernous hemangioma of the kidney preoperatively. This case is unusual because the configuration of this tumor changed within a few years. When we find a renal cyst with a solid component, renal cavernous hemangioma arising from the cyst wall should be considered in the differential diagnosis, and a conservative surgical approach should be considered.

A 70-year-old woman who underwent proximal gastrectomy for gastric cancer (poorly-differentiated adenocarcinoma) of Stage IIIB at age 46 visited our hospital April 2004 because of exacerbated pain by movement in the buttocks since November 2003. She showed multiple bone metastasis by CT (computerized tomography). Pancreas cancer or gallbladder cancer was suspected by CT, and a high tumor marker score (CA19-9 18,625 U/mL, DUPAN-II 15,000 U/ mL elevations were acknowledged). Although her symptoms were severe with performance status (PS) 4, she was administered combination chemotherapy with gemcitabine and cisplatin. After 2 cycle therapy, her PS was improved to 2, but the tumor markers had elevated. So we changed the chemotherapy menu to S-1 and gemcitabine. Her tumor markers lowered and PS was improved to 1. There was a remarkable response to this chemotherapy, and the result of CT and bone scintigraphy suggested that her bone metastasis was improved. Because of hematologic relapse due to DIC at 1 year after the first treatment, she was readmitted to our hospital and later died. The autopsical result revealed recurrence of gastric cancer 23 years post-operatively.

Background/aims: From 1992 to 2003, 7 carcinomata in situ (CIS) were incidentally discovered during microscopical observation of resected materials for advanced carcinomas of peripancreatic organs, of which 4 had undergone endoscopic retrograde cholangiopancreatography (ERCP) or postoperative pancreatography of the resected specimen (POP). In addition, 7 of 79 invasive ductal carcinomata (IDC) of the pancreas were accompanied by CIS > or =2 cm long. A total of 11 patients were reviewed here for pancreatographic findings for CIS of the pancreas., Methods: All resected pancreatobiliary materials were sliced serially at 5- to 8-mm intervals in a plane at right angles to the main pancreatic duct, referring to POP images., Results: Irregularity (I), non-continuous narrowing (N), granular defects (G), and dilatation (D) were seen in 78, 67, 33 and 22% on ERCP, respectively, and in 90, 70, 60 and 40% on POP, respectively., Conclusions: I, N, G, and D are most important pancreatographic findings in ERCP and highly suggestive of CIS of the pancreas, so that whenever they are encountered, cytological and/or pathological examination of the pancreatic duct should be actively performed., (Copyright 2008 S. Karger AG, Basel.)

Objective: Irritable bowel syndrome is characterized by abdominal discomfort and/or pain associated with altered bowel habits. The neurotransmitter serotonin and serotonin type 3 receptors that are extensively distributed on enteric neurons in the human gastrointestinal tract play a role in increasing the sensation of pain and affecting bowel habits in patients with irritable bowel syndrome. The aim of this study was to evaluate the efficacy and safety of the serotonin type 3 receptor antagonist ramosetron hydrochloride in Japanese patients with diarrhea-predominant irritable bowel syndrome., Material and Methods: In a double-blind, placebo-controlled, parallel group-comparative study with a 1-week run-in period, 539 patients with diarrhea-predominant irritable bowel syndrome meeting the Rome II diagnostic criteria received either 5 microg ramosetron hydrochloride (n=270) or placebo (n=269) once daily for 12 weeks., Results: Forty-seven percent of ramosetron hydrochloride-treated patients were monthly responders in the primary end-point, "Patient-reported global assessment of relief of irritable bowel syndrome symptoms", compared with 27% for placebos (p<0.001). The most frequently reported adverse event in the ramosetron hydrochloride-treated group compared with the placebo group was hard stool., Conclusions: Ramosetron hydrochloride 5 microg once daily is effective and well tolerated in the treatment of abdominal pain, discomfort and bowel habits in patients with diarrhea-predominant irritable bowel syndrome.

Background & Aims: The mortality rate associated with severe acute pancreatitis (SAP) with necrosis remains high because early prediction of pancreatic necrosis is difficult. We evaluated whether perfusion computerized tomography (CT), which is used to identify early stage ischemia in the brain, could detect ischemic changes in the pancreas in the early stages of SAP and predict development of necrosis., Patients and Methods: Thirty consecutive patients with a diagnosis of SAP according to the Atlanta criteria and whose score was greater than 6 were enrolled in this study. All patients were hospitalized within 3 days after onset of symptoms indicative of acute pancreatitis and underwent perfusion CT. Three weeks later, all patients underwent conventional contrast-enhanced CT to detect progression of their disease., Results: Perfusion CT showed that 10 of the 30 patients had pancreatic ischemia at the time of diagnosis. Contrast-enhanced CT disclosed that pancreatic necrosis developed in 9 of these 10 patients, but not in the 20 patients who did not have pancreatic ischemia. The sensitivity and specificity of perfusion CT for predicting pancreatic necrosis was calculated to be 100% and 95.3%, respectively., Conclusions: Perfusion CT is a useful tool for early detection of ischemic changes in the pancreas that lead to pancreatic necrosis.

Corticotropin-releasing factor (CRF) and urocortin I (UcnI) have been shown to accelerate colonic transit after central nervous system (CNS) or peripheral administration, but the mechanism of their peripheral effect on colonic motor function has not been fully investigated. Furthermore, the localization of UcnI in the enteric nervous system (ENS) of the colon is unknown. We investigated the effect of CRF and UcnI on colonic motor function and examined the localization of CRF, UcnI, CRF receptors, choline acetyltransferase (ChAT), and 5-HT. Isometric tension of rat colonic muscle strips was measured. The effect of CRF, UcnI on phasic contractions, and electrical field stimulation (EFS)-induced off-contractions were examined. The effects of UcnI on both types of contraction were also studied in the presence of antalarmin, astressin2-B, tetrodotoxin (TTX), atropine, and 5-HT antagonists. The localizations of CRF, UcnI, CRF receptors, ChAT, and 5-HT in the colon were investigated by immunohistochemistry. CRF and UcnI increased both contractions dose dependently. UcnI exerted a more potent effect than CRF. Antalarmin, TTX, atropine, and 5-HT antagonists abolished the contractile effects of UcnI. CRF and UcnI were observed in the neuronal cells of the myenteric plexus. UcnI and ChAT, as well as UcnI and 5-HT, were colocalized in some of the neuronal cells of the myenteric plexus. This study demonstrated that CRF and UcnI act on the ENS and increase colonic contractility by enhancing cholinergic and serotonergic neurotransmission. These peptides are present in myenteric neurons. CRF and, perhaps, to a greater extent, UcnI appear to act as neuromodulators in the ENS of the rat colon.

Hepatic arterial infusion chemotherapy employs a hepatic artery catheter as a conduit to achieve a high concentration of antineoplastic agents to liver tumors. Historically, this catheter placement has been performed via laparotomy. However, it may now be performed using less-invasive percutaneous image guided procedures. There are many anatomical hepatic arterial variations and complicated blood flow patterns. Various techniques are required to ensure high concentration of antineoplastic agents in liver tumors. These techniques are composed of arterial redistribution by embolization, percutaneous catheter placement applying "tip-fixation method," and evaluation and management of flow patterns that reflect drug distribution. The role of interventional radiologists in hepatic arterial infusion chemotherapy is to create and manage the access to achieve these objectives.

Hepatic arterial infusion chemotherapy (HAIC) for liver metastases from digestive cancer has passed through a long history. In spite of its significant high tumor reduction rate, this therapeutic modality has been rejected as the first-line therapy for liver metastases from colorectal cancer because of the negative results of RCTs compared to systemic chemotherapy. However, recently some excellent results have been reported by the combination with systemic chemotherapy,and a positive result of RCT using a satisfactory study design has been reported. Thus, the combination with systemic chemotherapy and RCT in comparison with modern standard systemic chemotherapy as the first-line therapy remains an important problem to be solved. On the other hand, the highly-developed technology for HAIC using techniques of interventional radiology has been standardized in Japan. Thus, we now have become the closest in the world to performing good-quality clinical trials of HAIC supported by high-quality technology. We should therefore consider our very important role in resolving such problems and deciding the future of HAIC.

Rome I diagnostic criteria for IBS was published in 1992 and it became a global diagnostic criteria. However, the criteria was not practical and somewhat complicated. Moreover, its symptomatic duration was too long (defined as more than 3 months) to be introduced in clinical practice. Therefore, Japanese member of BMW(Bowel Motility Workshop) tried to develop a new diagnostic criteria for IBS and it was established in 1995 by way of the Delphi method. The criteria was named as BMW diagnostic criteria and it was shown below: BMW diagnostic criteria for IBS (1995) At least one month or more of repetitive symptoms of the following 1) and 2) and no evidence of organic disease that likely to explain the symptoms. 1) Existence of abdominal pain, abdominal discomfort or abdominal distension 2) Existence of abnormal bowel movement (diarrhea, constipation) Abnormal bowel movement includes at least one of the below; (1) Abnormal stool frequency (2) Abnormal stool form (lumpy/hard or loose/wartery stool) Moreover, the following test should be performed as a rule to exclude organic diseases. (1) Urinalysis, fecal occult blood testing, CBC, chemistry (2) Barium enema or colonofiberscopic examination The other diagnostic criteria for IBS was also reviewed and their characteristics were compared with BMW diagnostic criteria.

A 37-year-old man underwent Miles' operation and adjuvant irradiation therapy for rectum cancer in 1999. The patient suffered from bilateral ureteral stricture after the previous therapies. Bilateral double-J ureteral stents were inserted and exchanged at regular intervals. Four years after the start of ureteral stenting, he complicated with gross hematuria and dysuria. When the right double-J stent was exchanged, massive bleeding from external opening of urethra was observed. Retrograde pyelography showed right uretero-iliac arterial fistula. Since endovascular treatment with covered stents had failed, we performed right common iliac artery embolization and femoral-femoral artery bypass. Two days after the operation, gross hematuria developed again. When the left ureteral stent was exchanged, active bleeding from the external meatus of urethra was revealed. Angiography showed extravasation from left common iliac artery. We diagnosed left uretero-iliac arterial fistula. Although we tried endovascular treatment with covered stent that was made of artificial vessel graft and metallic stent, thromboembolism was occurred in the covered stent. Finally, right axillo-femoral artery bypass was indicated. The last treatment achieved long-term good control of uretero-arterial fistula. The present case shows that uretero-arterial fistula is a serious complication of long-term ureteral stenting, especially in the case of post pelvic surgery and irradiation.

This document addresses the design of trials to assess the efficacy of new treatments for functional gastrointestinal disorders (FGID), emphasizing trials in irritable bowel syndrome and dyspepsia, because most research has been undertaken in these conditions. The double-blind, randomized, placebo-controlled, parallel group trial remains the preferred design. Randomized withdrawal designs, although encouraged by the European Agency for the Evaluation of Medicinal Products, have the same potential disadvantages as a crossover design, including carryover effects, unmasking (unblinding), and overestimation of the potential benefit for clinical practice. Innovative trial designs that evaluate intermittent (on demand) treatment are likely to become more common in the future. Investigators should include as broad a spectrum of patients as possible and should report recruitment strategies, inclusion/exclusion criteria, and attrition data. The primary analysis should be based on the proportion of patients in each treatment arm who satisfy an a priori treatment responder definition, or a prespecified clinically meaningful change in a patient-reported symptom improvement measure. Such measures of improvement are psychometrically validated subjective global assessments or a change from baseline in a validated symptom severity questionnaire. It is unethical to change the responder definition after a trial begins. Data analysis should address all patients enrolled, using an intention-to-treat principle. Reporting of results should follow the Consolidated Standards for Reporting Trials guidelines and include an analysis of harms data and secondary outcome measures to support or explain the primary outcome. Trials should be registered in a public location, prior to initiation, and should be published even if the results are negative or inconclusive.

Background: It is well known that pancreatic cancer is rarely cured and is usually fatal. The clinicopathological features of small (greatest dimension < or = 2 cm by histologic measurement) carcinoma of the pancreas (s-PC), were reviewed, paying special attention to new computed tomography (CT) finding that suggests the presence of s-PC., Methodology: Sixteen patients with s-PC have undergone curative surgery at Aichi Cancer Center Hospital during the past 11 years. Their preoperative diagnostic findings, pathological findings and postoperative prognoses were analyzed., Results: The most useful diagnostic clue was dilatation of the main pancreatic duct (MPD). It was difficult to identify the tumor in four patients because of pancreatitis accompanying the MPD obstruction. In three of these four cases, early phase-enhanced CT revealed a contrasting effect between the proximal and distal sides of the pancreatic parenchyma at the site of the MPD obstruction (black & white sign). The longest diameters of the tumors ranged from 0.9 to 2 cm (average 1.3 cm). Positive rates of capsular invasion, retroperitoneal invasion, and lymph node metastasis were 6.3% (1/16), 31.3% (5/16), and 18.8% (3/16), respectively. Six patients (37.5%) were classed at stage I, six (37.5%) stage II, three (18.8%) stage III, and one (6.2%) at stage IV according to pathological TNM classification. One patient died of the disease, and the cumulative 3- and 5-year survival rates were 88.9% and 59.3%, respectively., Conclusions: The presence of s-PC qualifies as early PC and has a good prognosis. The CT black + white sign will be useful in the diagnosis of s-PC accompanying pancreatitis.

Transcatheter arterial embolization was attempted for external iliac artery (EIA) hemorrhage in five patients with wound infection after pelvic malignant tumor surgery. To prevent distal migration of coils and to preserve distal branches of the EIA, the entire weakened artery was occluded with use of coils via a bilateral femoral artery approach with balloon occlusion of the distal side. The success rate was 100%. No limb loss was observed immediately after embolization. This method can prevent distal migration of coils and preserve branches that can be collaterals to the femoral artery, and as such it can be used to embolize an adequate portion of the affected artery.

The case of a patient who developed intractable massive ascites caused by hepatic lymphorrhea derived from surgical injury to the hepatoduodenal ligament is presented. OK-432 was injected intraperitoneally through a catheter advanced to near the hepatoduodenal ligament, so as to expose this site to a high concentration of OK-432. Under ultrasound guidance, it was difficult to reach this site due to massive ascites, and so we performed this procedure under CT and fluoroscopic guidance using a unified CT and angiography system. Subsequently, local administration of OK-432 on five separate occasions resulted in resolution of the ascites. We ascribe this favourable result to the use of this unified CT and angiography system to advance the catheter to the suitable site, making possible the local administration of OK-432.

In imaging diagnosis of metastatic liver neoplasms, particularly in preoperative evaluation, it is necessary to detect all lesions, note involved hepatic segments, determine relations with intrahepatic vascular structure, evaluate local invasiveness of lesions, and exclude the presence of extrahepatic metastases. Various imaging features can be demonstrated with appropriate imaging techniques and provide useful information for differential diagnosis or determination of the primary site. Multip lemodalities such as ultrasonography, computed tomography (CT), magnetic resonance imaging (MRI), and angiography including CT during arterial portography and CT during hepatic arteriography are used for the diagnosis of metastatic liver neoplasms, and it is important to know the characteristics of each. Among the advances in imaging technology, the practical use of super-paramagnetic iron oxide-enhanced MRI (SPIO-enhanced MRI) has had a major impact. SPIO-enhanced MRI is a promising imaging modality for the detection of metastatic liver neoplasms because of its relatively high sensitivity and extremely high specificity. Accumulation of additional results is still necessary, but the imaging strategy for metastatic liver neoplasms will likely be based mainly on SPIO-enhanced MRI in the future.

Purpose: To investigate the technical outcome of radiologic catheter placement with use of a side-hole catheter with distal fixation for hepatic arterial infusion chemotherapy., Materials and Methods: Between January 1993 and September 1999, 426 patients were referred to our department to undergo intraarterial infusion chemotherapy for unresectable malignant liver tumors. A subclavian artery was exposed under local anesthesia and a catheter was inserted. After inserting the tip of the side-hole catheter into the gastroduodenal artery, splenic artery, or peripheral branch of the hepatic artery, the catheter tip was fixed to the vessel with use of coils and a mixture of n-butyl cyanoacrylate (NBCA) and iodized oil. The proximal end of the catheter was connected to an implanted port, and the port system was embedded subcutaneously., Results: Placement was successful in 425 of 426 patients (99.8%) in a mean time of 76 minutes. Catheter dislodgement was noted in 12 patients (2.8%). Cumulative patency rates of the hepatic artery calculated according to the Kaplan-Meier method for the entire group were 91.0%, 81.4%, and 58.1% at 6 months and 1 and 2 years, respectively. Complications related to catheter placement were observed in nine cases and included dysfunction of the implanted system (n = 3), significant bleeding around the implanted port (n = 2), improper infusion of NBCA and iodized oil (n = 2), and cerebral infarction (n = 2)., Conclusion: Radiologic catheter placement via a subclavian artery with side-hole catheter placement with distal fixation for hepatic arterial infusion chemotherapy is a highly successful procedure with a reduced risk of catheter dislodgment and arterial occlusion.

Bare stents are commonly used for the treatment of malignant vena cava stenoses. However, the therapeutic effect of treatment using bare stents for cases with intraluminal tumor invasion is not satisfactory. We report a case with severe obstruction of the superior vena cava caused by tumor invasion of mediastinal lymph node metastases from colon cancer, which was successfully treated by the recanalization of superior vena cava using a polytetrafluoroethylene-covered Z stent. The covered stent could not be fully expanded at first, and re-obstruction developed at the stented site due to thrombus formation soon after stenting. So, the additional balloon dilatation made the stent expend fully on another day of stenting. After the balloon dilatation blood flow improved immediately and the clinical symptoms associated with the superior vena cava obstruction resolved. Thereafter no symptomatic recurrence has been observed in 12 months of follow-up period.

Previous clinical trials have shown a significantly higher tumor response to arterial infusion chemotherapy for liver metastases compared with systemic chemotherapy, but failed to show the survival impact. Thus, there has been no evidence to justify the use of this therapy for liver metastases. On the other hand, the results of previous clinical trials cannot be used to decide the role of this therapy, because the trials were performed under incomplete situations in which there was no consideration of the unreliability of imaging diagnoses and the importance of techniques. At present, therefore, we should use this therapy based on deep understanding and thought toward previous data and patients' conditions. Clinical trials involving considerations for this special therapy are required in order to decide the role of this therapy.

Purpose: The purpose of the study was to investigate the technical outcome and clinical effect of right gastric artery (RGA) embolization to prevent acute gastric mucosal lesions caused by influx of anticancer agents into the RGA in patients undergoing repeat hepatic arterial infusion chemotherapy (HAIC)., Materials and Methods: In 217 patients with malignant hepatic tumors, we attempted RGA embolization with use of metallic coils and/or a mixture of n-butyl cyanoacrylate (n-BCA) and iodized oil, along with the embolization of the gastroduodenal artery. After this procedure, an infusion catheter was placed radiologically and HAIC was performed. We then evaluated the technical outcome and clinical effect of RGA embolization., Results: RGA embolization was technically successful in 201 of 217 patients (93%). Major complications--nausea, epigastric pain, and fever--were noted in 12%, 4%, and 2% of successful cases, respectively, and were treated conservatively. Recanalization occurred in 4% (nine of 201) of the patients. Eventually, sufficient RGA embolization was achieved in 192 patients. The incidence of acute gastric mucosal lesions confirmed endoscopically was only 3% (five of 192) in patients with sufficient RGA embolization, whereas it was 36% (nine of 25) in patients without sufficient RGA embolization, with a significant difference (P <.01)., Conclusion: RGA embolization is a highly feasible procedure that can reduce the incidence of acute gastric mucosal lesions associated with HAIC.

Background: Several studies have reported that the chimeric monoclonal antibody to tumor necrosis factor (TNF)-alpha (Infliximab) is extremely valuable in the treatment of Crohn's disease. The aim of this study was to clarify the efficacy of this treatment in Japanese patients with Crohn's disease., Methods: A 12-week multicenter, open trial of Infliximab was carried out and involved 25 patients with moderate to severe Crohn's disease who were resistant to conventional treatment. Patients received a single 2-h intravenous infusion of Infliximab at a dose of 1, 3, 5 or 10 mg/kg bodyweight. Clinical evaluation of this treatment response was defined as a reduction in the index of the inflammatory bowel disease (IOIBD) and of the Crohn's disease activity index scores (CDAI), and in serum levels of C-reactive protein (CRP) at 2, 4, 8 and 12 weeks, and as an increase in serum levels of rapid turnover proteins as well as improvement of radiologic and endoscopic findings at 4 weeks., Results: The IOIBD score was reduced after 4 weeks in 66.7% of the group receiving 1 mg/kg Infliximab, 71.4% in the group receiving 3 mg/kg, 80.0% in the group receiving 5 mg/kg, and 85.7% in the group receiving 10 mg/kg. Improvement was better maintained over 12 weeks in the 5 and 10 mg/kg groups compared with the 1 and 3 mg/kg groups. Similar results were obtained for the CDAI scores. Serum levels of rapid turnover proteins significantly increased to within the normal ranges after infusion in all groups. Seven of the 11 (63.6%) patients evaluated showed improvement of radiologic and endoscopic findings., Conclusions: A single infusion of Infliximab was effective for the treatment of Japanese patients with Crohn's disease. Serum rapid turnover proteins reflected the clinical response to antibody for TNF-alpha well.

We report two cases in which hepatic arterial occlusion developed soon after percutaneous catheter placement for hepatic arterial infusion chemotherapy in malignant hepatic neoplasms. A replaced hepatic artery and a proper hepatic artery, respectively, became occluded in these cases. In both, because the tip of a side-holed catheter for arterial infusion was fixed in place, we performed recanalization without removing the indwelling catheter. Despite the presence of the catheter, a stent could be inserted into the occluded portion of the hepatic artery. Recanalization of the hepatic artery was achieved with stent placement, and continuation of hepatic arterial infusion became possible.

Endoscopic biliary drainage (EBD) for unresectable hepatocellular carcinoma (HCC) associated with obstructive jaundice remains controversial because of the short survival of these patients. To evaluate the effectiveness of this procedure, we retrospectively studied 18 patients who had unresectable HCC with obstructive jaundice and underwent EBD with polyethylene stents, over a 10-year period. Nine patients with tumor thrombus involving the first branches of the portal vein or portal trunk (Vp3) formed group A and the other 9 (Vp0-Vp2) formed group B. The serum albumin level and serum total bililubin level differed significantly between the two groups (P < 0.05 and P < 0.005. Student's t-test), but prothrombin time did not. The obstructive jaundice was mainly caused by direct tumor invasion in 6 patients from group A and 3 from group B, by blood clots and/or tumor fragments in 2 patients from group A and 3 from group B, by the tumor protruding into the common hepatic duct in 2 patients from group B. and by tumor compression of the common bile duct in 1 patient from each group. Drainage was successful in 4 patients (44%) from group A and in all 9 patients (100%) from group B. Among the 5 patients with unsuccessful drainage in group A, 4 had obstruction of both the left and right hepatic ducts and 3 had multiple tumors in both lobes. The mean survival time (mean +/- SD) after EBD was 47 +/- 44 days in group A and 181 +/- 70 days in group B. In group A. the average survival time was only 85 days in the 4 patients with successful drainage. However, an improvement in the quality of life after EBD was observed in one-third of the Vp3 patients and in all of the Vp0-Vp2 patients. In summary, satisfactory palliation is possible with successful EBD, but this is difficult in most patients with Vp3 portal thrombus, direct tumor invasion involving both hepatic ducts, and multiple tumors in both lobes. It is important to determine the site, extent, and nature of the obstruction, as well as liver function and the presence of portal thrombus, before performing EBD.

Aims: The purpose of our study was to evaluate the observer performance with combined helical CT during arterial portography (CTAP) and biphasic CT hepatic arteriography (CTHA) in the pre-operative detection of malignant hepatic tumours., Methods: Computed tomography images obtained in 41 patients with suspected hepatic tumours were retrospectively reviewed. In a blind fashion, three off-site, independent radiologists reviewed CTAP and early-phase CTHA combined for the first review, then late-phase CTHA was added for the second review. Statistical analysis was conducted on lesion-by-lesion and segment-by-segment bases; a total of 328 liver segments including 65 segments with 74 malignant hepatic tumours ranging in size from 5 to 100 mm (mean, 21.4 mm) were analysed., Results: Sensitivity for detection of liver segments harbouring tumours of CTAP and biphasic CTHA combined (82%) was identical to that of CTAP and early-phase CTHA combined (82%). Specificity of CTAP and biphasic CTHA combined (93%) was greater than that of CTAP and early-phase CTHA combined (90%, P < 0.005). The mean confidence level for the 74 tumours significantly increased by adding late-phase CTHA (P < 0.0005). The mean confidence level for 100-142 benign perfusion abnormalities detected with CTAP and early-phase CTHA combined significantly decreased by adding late-phase CTHA (P < 0.0005)., Conclusion: By combining late-phase CTHA with CTAP and early-phase CTHA information, the specificity for the detection of malignant hepatic tumours rises significantly, allowing more accurate preoperative tumour detection., (Copyright 2001 The Royal College of Radiologists.)

Purpose: To investigate the efficacy of computed tomography (CT) fluoroscopy and a new needle holder (the I-I device) in lung nodule biopsy., Materials and Methods: The I-I device is made of acrylate resin and was used to keep the entire needle in the tomographic plane. This study consisted of biopsies of 79 lung nodules in 77 patients. The final diagnoses were malignant in 54 patients, benign in 23, and unconfirmed in two. The biopsy procedure time from the beginning of the CT fluoroscopy procedure to the removal of the needle was measured for 24 needle passes. The radiation dose on the physician's hand was measured in five cases with use of a thermoluminescence ring., Results: Fifty-one malignant and 20 benign lesions were correctly diagnosed with histologic specimens (90%). In 58 of 77 patients (75%), the biopsy procedures were completed within a single breath-hold. Pneumothorax occurred in 20 of 77 patients (26%) and chest tube insertion was required in five. The incidence of pneumothorax was significantly lower in patients who held their breath during biopsy procedures compared with those who did not (P < .0001; chi2 test). The biopsy procedure time ranged from 15 to 39 seconds (mean: 28.2 sec). The mean radiation dose on the physician's hand was 2 mSv/case., Conclusion: The diagnostic accuracy of biopsy with use of the I-I device under CT fluoroscopic guidance is comparable with that of the conventional method; however, a combination of CT fluoroscopy and the I-I device enables rapid biopsy procedures.

Prostaglandin (PG) and nitric oxide (NO) have been known to inhibit the lesion formation induced by necrotic agents. However, no clear correlation between PG and NO has been shown in the gastroprotective action against necrotic agent-induced gastric mucosal lesions in rats. Thus, the present study was performed to clarify this correlation. Gastric mucosal lesions were induced by the oral administration of 0.6 M HCl in rats. 16,16-Dimethyl PGE2 (0.3-3 microg/kg, p.o.; dim-PGE2), sodium nitrite (0.3 and 1 mg/kg, s.c.) and sodium nitroprusside (30 and 100 microg/kg, i.v.; SNP) dose-dependently inhibited the lesion formation. Orally administered sodium nitrite or SNP (3 mg/kg) also significantly inhibited the lesion formation. The gastroprotective action by dim-PGE2 was not affected by the pre-treatment with N(G)-nitro-L-arginine methylester (10 mg/kg, i.v.). The gastroprotective effect by sodium nitrite or SNP was markedly attenuated by the pre-treatment with indomethacin (10 mg/kg, s.c.). These findings suggest that NO donating compounds inhibit the HCl-induced mucosal lesions mainly through prostaglandin, but dim-PGE2 directly inhibits the lesions without involvement of NO in rats.

Active ulcerative colitis (UC) is characterized by activation and infiltration of granulocytes and monocytes/macrophages into the colonic mucosa. The infiltrated leukocytes can cause mucosal damage by releasing degradative proteases, reactive oxygen derivatives, and proinflammatory cytokines. The aim of this trial (conducted in 14 specialist centers) was to assess safety and efficacy of granulocyte and monocyte adsorption apheresis in patients with active UC most of whom were refractory to conventional drug therapy. We used a new adsorptive type extracorporeal column (G-1 Adacolumn) filled with cellulose acetate beads (carriers) of 2 mm in diameter, which selectively adsorb granulocytes and monocytes/macrophages. Patients (n = 53) received five apheresis sessions, each of 60 minutes duration, flow rate 30 ml per minute for 5 consecutive weeks in combination with 24.4 +/- 3.60 mg prednisolone (mean +/- SE per patient per day, baseline dose). During 60 minutes apheresis, 26% of granulocytes, 19.5% of monocytes and 2% of lymphocytes adsorbed to the carriers. At week 7, 58.5% of patients had remission or improved, the dose of prednisolone was reduced to 14.2 +/- 2.25 mg (n = 37). The apheresis treatment was fairly safe, only eight non-severe side effects (in 5 patients) were reported. Based on our results, we believe that in patients with active severe UC, patients who are refractory to conventional drugs, granulocyte and monocyte adsorption apheresis is a useful adjunct to conventional therapy. This procedure should have the potential to allow tapering the dose of corticosteroids, shorten the time to remission and delay relapse.

Background: Serotonin (5-HT) may play an important role in the regulation of colonic motility in humans. However, it is not known whether alterations in the colonic 5-HT system are involved in the pathophysiology of irritable bowel syndrome (IBS)., Methods: Colonic mucosal specimens ranging from the ascending colon to the rectum were obtained from patients with diarrhea- or constipation-predominant IBS (n = 7 and n = 8, respectively) and from subjects with normal bowel habits (n = 7) by endoscopic biopsy in order to determine whether patients with different clinical manifestations of IBS have different mucosal disposition of 5-HT. The tissue concentrations of 5-HT and its major metabolite, 5-hydroxyindoleacetic acid, were determined by reversed-phase high-performance liquid chromatography with fluorescence detection., Results: In all study groups, the mean mucosal 5-HT concentrations obtained from the rectum were significantly (p < 0.05) higher than those obtained from more cephalic regions of the colon. In addition, the overall mean mucosal 5-HT concentrations obtained from patients with constipation-predominant IBS were significantly (p < 0.05) higher than those obtained from the control subjects and patients with diarrhea-predominant IBS. No significant differences were observed in 5-hydroxyindoleacetic acid concentrations among the three groups., Conclusions: The mucosal 5-HT concentrations in the colon showed an ascending cephalocaudal gradient in all study groups. Although the mucosal 5-HT concentrations were elevated in patients with constipation-predominant IBS as compared with those with diarrhea-predominant IBS and the control subjects, further studies are necessary to determine whether the elevated mucosal 5-HT is a cause or a result of abnormal colonic motility., (Copyright 2001 S. Karger AG, Basel)

After randomized studies of hepatic arterial infusion chemotherapy (HAIC) versus systemic chemotherapy for liver metastases from colorectal cancer in the 1980s, the role of HAIC has been unclear and there is still no evidence to support it as the treatment of choice. The high local control, the differences in techniques between Japan and Western countries, the difficulty of detecting pre-treatment extra-hepatic metastases and the fact that HAIC does not control extra-hepatic lesions are the most important points in considering clinical trials of HAIC. Clinical studies on the combination of HAIC using 5-FU and systemic chemotherapy using CPT-11, and then randomized trial of systemic chemotherapy with/without HAIC is required in Japan to reveal the role of HAIC in the management of liver metastases from colorectal cancer. We should understand the importance of our role in this field.

CT-guided lung biopsy is now widely performed for tumorous lesions in the lung, and both its usefulness in this context and the associated complications have been well described in the literature. Although severe complications are rare, we describe a case in which massive intrathoracic haemorrhage developed after lung biopsy and necessitated emergency operation for control. Intraoperative findings suggested that the source of the haemorrhage was a fibrous, cord-like substance present at the site of adhesion associated with old tuberculosis. We attributed this haemorrhage to a pneumothorax, which developed after lung biopsy and caused the new vessels penetrating the centre of the fibrous, cord-like substance to stretch and rupture. Numerous cases have been reported of spontaneous haemopneumothorax precipitated by spontaneous pneumothorax and resulting from the rupture of such vessels.

The causes of non-tumorous abnormalities in the hepatic hilum seen on CT hepatic arteriography were investigated. 13 patients with non-tumorous defects of portal perfusion in the hepatic hilum on CT arterial portography underwent both CT hepatic arteriography from the common hepatic artery and CT obtained during proper hepatic arteriography. The findings of non-tumorous portal defects on these two angiographic studies using helical CT were compared. In the 13 patients, 14 non-tumorous defects of portal perfusion in the hepatic hilum on CT arterial portography were detected as enhanced areas in 10 regions (dorsum of segment IV, 7/10; dorsum of the lateral segment, 3/4) on CT hepatic arteriography via the common hepatic artery, but none were enhanced on CT obtained during proper hepatic arteriography. In conclusion, the main cause of non-tumorous enhancement in the hepatic hilum seen on CT hepatic arteriography is non-portal direct inflow via the parabiliary venous system.

Objective: The purpose of our study was to evaluate the use of combined helical CT during arterial portography and CT hepatic arteriography in the preoperative assessment of hepatic metastases from colorectal cancer using a unified CT and angiography system., Materials and Methods: Fifty-four patients with hepatic metastases from colorectal cancer preoperatively underwent combined CT during arterial portography and CT hepatic arteriography using the unified CT and angiography system. Three radiologists independently and retrospectively reviewed the images of CT during arterial portography alone, CT hepatic arteriography alone, and combined CT during arterial portography and CT hepatic arteriography. Image review was conducted on a segment-by-segment basis; a total of 432 hepatic segments with (n = 103) 118 metastatic tumors ranging in size from 2 to 160 mm (mean, 25.8 mm) and without (n = 329) tumor were reviewed., Results: Relative sensitivity of combined CT during arterial portography and CT hepatic arteriography (87%) was higher than that of CT during arterial portography alone (80%, p < 0.0005) and CT hepatic arteriography alone (83%, p < 0.005). Relative specificity of CT hepatic arteriography alone (95%, p < 0.0005) and combined CT during arterial portography and CT hepatic arteriography (96%, p < 0.0001) was higher than that of CT during arterial portography alone (91%). Diagnostic accuracy, determined by a receiver operating characteristic curve analysis, was greater with combined CT during arterial portography and CT hepatic arteriography than with CT during arterial portography alone (p < 0.05) or CT hepatic arteriography alone (p < 0.01)., Conclusion: Using a unified CT and angiography system, we found that combined CT during arterial portography and CT hepatic arteriography significantly raised the detectability of hepatic metastases from colorectal cancer.